These studies are designed to investigate the enhanced rate of benzo(alpha)pyrene metabolism following interaction of cytochrome P-448 obtained from TCDD treated rats with hepatic and renal microsomes low in endogenous cytochrome P-450 and MFO enzyme activity. TCDD is known to produce teratogenesis and fetal lethality in mammals as well as porphyria in a variety of species. TCDD also increases the activation of various exogenous carcinogenic hydrocarbons and alters the metabolism of endogenous steroid hormones in mammalian tissues. The present studies demonstrate that aryl hydrocarbon hydroxylase activity was increased 12, 26, 31 and 53 fold when 1.0 nmole of partially purified cytochrome P-448 was incubated with fetal liver microsomes, microsomes from kidney cortex of female rats and cumene hydroperoxide pretreated hepatic microsomes from female and male rats, respectively. CHP pretreatment increased both the absolute magnitude of and the relative increase in enhanced AHH rate in adult rat hepatic microsomes incubated with cytochrome P-448, while CHP pretreatment decreased these parameters in fetal hepatic and adult renal microsomes. Incubation with 1 nmole of exogenous cytochrome P-448 increased the AHH activity of NADPH-treated, lipid peroxidized microsomes by 76 fold, a value 20% higher than control microsomal AHH activity.